SPECIFIC AIMS[unreadable] We proposed that changes in the energetic cost of walking is implicated in the causal pathway that leads to progressive functional decline and disability in older persons. The deterioration of efficiency of the human machine, the reduce availability of residual energy for movement, the impairment of the homeostatic mechanisms that optimize energy production and, finally, the development of fatigue at low levels of activity may constitute the elements of a causal pathway leading to sedentary behavior and progressive disability. [unreadable] According to our hypothesis, excessive fatigue relative to the degree of physical activity may arise from different, but potentially synergic mechanisms: [unreadable] - increased RMR due to high cost of homeostasis and dysregulation or malfunction of the homeostatic network (due to both acute and chronic diseases processes); [unreadable] - increased energetic cost of mobility due to increased biomechanical inefficiency and decline in the anatomical integrity and harmonic function of the "human ambulatory machine"; [unreadable] - compromised energy availability , due to specific pathological processes, CHF for instance, and/or inefficient transport of energy to the required sites, mainly due to reduced homeostatic ability.[unreadable] [unreadable] RESEARCH PLAN[unreadable] To test the hypothesis high energetic cost of walking, increased RMR and and development of fatigue at low levels of activity are key predictor of disability, we propose to explore the relationship between RMR, the energetic and mechanical aspects of walking (gait lab) and the threshold for the development of fatigue in the participants of the BLSA..[unreadable] [unreadable] Outcomes of the study[unreadable] Primary outcome: to evaluate whether higher RMR, high energetic cost of walking, and a dysregulation of the energy homeostatic network (level of inflammatory markers and hormones) are independent predictors of energetic threshold for the development of subjective fatigue.[unreadable] Secondary outcome: to verify whether information on RMR, energetic cost of walking and dysregulation of the energy homeostatic network provide information on fitness and fatigability independent of the measure of fitness provided by a standard treadmill test;[unreadable] [unreadable] Study population[unreadable] Participants will consist of all BLSA participants. No exclusion criteria are established a priori. We seek to routinely measure oxygen consumption at rest, during normal walking and prolonged walking (400 m). Since portable equipment is already used during the normal testing, no additional time will be required to the BLSA scheduling of the participants.[unreadable] Threshold of fatigue will be estimated using Borg Scale. Each participant will be administered the Borg Scale at predetermined intervals during the physical task. [unreadable] [unreadable] Implementation of the BLSA to test the energetic pathway of disability[unreadable] We have introduced in BLSA measures of objective and subjective fatigue using the Borg Scale and the RQ ratio, respectively. This measurements will be performed at regular intervals during the tasks evaluating physical performance. In addition, we will be measuring metabolic rate using a portable equipment in different conditions, including rest, pre-exercise, customary walking, treadmill at low load and maximum load. Part of the study is to verify the hypothesis that change change in the circulating level of hormones, inflammatory markers, markers of oxidative stress and autonomic function modulates the relationship between workload, energy consumption and the development of fatigue.